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mitochondrial function

Shuting Cao, Huan Wu, ChunChun Wang, Qianhui Zhang, Lefei Jiao, Fanghui Lin, Caihong Hu
In the present study, we investigated the influence of diquat-induced oxidative stress on intestinal barrier, mitochondrial function and the level of mitophagy in piglets. Twelve male Duroc×Landrace×Yorkshire 35-d-old pigs (weaned at 21d of age), with an average body of 9.6 kg, were allotted to two treatments of six piglets each including the challenged group and the control group. The challenged pigs were injected with 100 mg/kg bodyweight diquat and control pigs injected with 0.9% (w/v) NaCl solution. The results showed that diquat injection decreased average daily feed intake and average daily gain...
March 17, 2018: Journal of Animal Science
Haijun Xiao, Yanghong Xu, Chenzi Ni, Qiannan Zhang, Feiya Zhong, Jishuai Huang, Wei Liu, Leilei Peng, Yingguo Zhu, Jun Hu
In flowering plants, various RNA editing events occur in the mitochondria and chloroplasts as part of post-transcriptional processes. Although several PPRs and MORFs have been identified as RNA editing factors, the underlying mechanism of PPRs and the cooperation among these proteins are still obscure. Here, we identified a rice dual-localized PPR protein, OsPGL1. The loss of function of OsPGL1 resulted in defects in both chloroplast RNA editing of ndhD-878 and mitochondrial RNA editing of ccmFc-543, both of which could be restored via complementary validation...
March 17, 2018: Journal of Experimental Botany
Suraiya Haroon, Annie Li, Jaye L Weinert, Clark Fritsch, Nolan G Ericson, Jasmine Alexander-Floyd, Bart P Braeckman, Cole M Haynes, Jason H Bielas, Tali Gidalevitz, Marc Vermulst
Genetic instability of the mitochondrial genome (mtDNA) plays an important role in human aging and disease. Thus far, it has proven difficult to develop successful treatment strategies for diseases that are caused by mtDNA instability. To address this issue, we developed a model of mtDNA disease in the nematode C. elegans, an animal model that can rapidly be screened for genes and biological pathways that reduce mitochondrial pathology. These worms recapitulate all the major hallmarks of mtDNA disease in humans, including increased mtDNA instability, loss of respiration, reduced neuromuscular function, and a shortened lifespan...
March 20, 2018: Cell Reports
Kate E R Hollinshead, Haydn Munford, Katherine L Eales, Chiara Bardella, Chunjie Li, Cristina Escribano-Gonzalez, Alpesh Thakker, Yannic Nonnenmacher, Katarina Kluckova, Mark Jeeves, Robert Murren, Federica Cuozzo, Dan Ye, Giulio Laurenti, Wei Zhu, Karsten Hiller, David J Hodson, Wei Hua, Ian P Tomlinson, Christian Ludwig, Ying Mao, Daniel A Tennant
Since the discovery of mutations in isocitrate dehydrogenase 1 (IDH1) in gliomas and other tumors, significant efforts have been made to gain a deeper understanding of the consequences of this oncogenic mutation. One aspect of the neomorphic function of the IDH1 R132H enzyme that has received less attention is the perturbation of cellular redox homeostasis. Here, we describe a biosynthetic pathway exhibited by cells expressing mutant IDH1. By virtue of a change in cellular redox homeostasis, IDH1-mutated cells synthesize excess glutamine-derived proline through enhanced activity of pyrroline 5-carboxylate reductase 1 (PYCR1), coupled to NADH oxidation...
March 20, 2018: Cell Reports
Carlos A Gómez, Jason Sutin, Weicheng Wu, Buyin Fu, Hana Uhlirova, Anna Devor, David A Boas, Sava Sakadžić, Mohammad A Yaseen
Investigating cerebral metabolism in vivo at a microscopic level is essential for understanding brain function and its pathological alterations. The intricate signaling and metabolic dynamics between neurons, glia, and microvasculature requires much more detailed understanding to better comprehend the mechanisms governing brain function and its disease-related changes. We recently demonstrated that pharmacologically-induced alterations to different steps of cerebral metabolism can be distinguished utilizing 2-photon fluorescence lifetime imaging of endogenous reduced nicotinamide adenine dinucleotide (NADH) fluorescence in vivo...
2018: PloS One
Nesibe Peker, Vinay Donipadi, Mridula Sharma, Craig McFarlane, Ravi Kambadur
Parkinson's Disease is a neurodegenerative disease characterized by tremors, muscle stiffness and muscle weakness. Molecular genetic analysis confirmed that mutations in PARKIN and PINK1 genes, which play major roles in mitochondrial quality control and mitophagy, are frequently associated with Parkinson's Disease. PARKIN is an E3 ubiquitin ligase that translocates to mitochondria during loss of mitochondrial membrane potential to increase mitophagy. Although muscle dysfunction is noted in Parkinson's Disease, little is known about the involvement of PARKIN in the muscle phenotype of Parkinson's Disease...
March 21, 2018: American Journal of Physiology. Cell Physiology
Ponarulselvam Sekar, Duen-Yi Huang, Shwu-Fen Chang, Wan-Wan Lin
Extracellular adenosine 5'-triphosphate (ATP) is a damage-associated molecular pattern and contributes to inflammation associated diseases including cancer. Extracellular acidosis is a novel danger signal in the inflammatory sites, where it can modulate inflammation, immunity and tumor growth. Extracellular acidification was shown to inhibit P2X7-mediated channel currents, while it remains unknown how acidification and P2X7 together affect cellular responses. Here, we treated BV-2 microglial cells with ATP in a short period (<15 min) or a sustained acidified condition...
February 27, 2018: Oncotarget
Steven A Harris, Elizabeth A Harris
This review focuses on research in the areas of epidemiology, neuropathology, molecular biology and genetics that implicates herpes simplex virus type 1 (HSV-1) as a causative agent in the pathogenesis of sporadic Alzheimer's disease (AD). Molecular mechanisms whereby HSV-1 induces AD-related pathophysiology and pathology, including neuronal production and accumulation of amyloid beta (Aβ), hyperphosphorylation of tau proteins, dysregulation of calcium homeostasis, and impaired autophagy, are discussed. HSV-1 causes additional AD pathologies through mechanisms that promote neuroinflammation, oxidative stress, mitochondrial damage, synaptic dysfunction, and neuronal apoptosis...
2018: Frontiers in Aging Neuroscience
Petrus Linge, Paul R Fortin, Christian Lood, Anders A Bengtsson, Eric Boilard
Dysregulation of lymphocyte function, accumulation of autoantibodies and defective clearance of circulating immune complexes and apoptotic cells are hallmarks of systemic lupus erythematosus (SLE). Moreover, it is now evident that an intricate interplay between the adaptive and innate immune systems contributes to the pathogenesis of SLE, ultimately resulting in chronic inflammation and organ damage. Platelets circulate in the blood and are chiefly recognized for their role in the prevention of bleeding and promotion of haemostasis; however, accumulating evidence points to a role for platelets in both adaptive and innate immunity...
March 21, 2018: Nature Reviews. Rheumatology
Ruifang Li, Ruiling Zhang, Yanhui Yang, Xueqin Wang, Yanjie Yi, Pei Fan, Zhengwei Liu, Chen Chen, Junpeng Chang
CGA-N12 is an antifungal peptide derived from human chromogranin A. In our previous investigation, CGA-N12 was found to have specific anti-candidal activity, though the mechanism of action remained unclear. Herein, we investigated the effects of CGA-N12 on mitochondria. We found that CGA-N12 induced an over-generation of intracellular reactive oxygen species and dissipation in mitochondrial membrane potential, in which the former plays key roles in the initiation of apoptosis and the latter is a sign of the cell apoptosis...
March 20, 2018: Biochemical Journal
Hailong Li, Zhongyuan Tang, Peng Chu, Yanlin Song, Ying Yang, Bin Sun, Mengyue Niu, Eskandar Qaed, Abdullah Shopit, Guozhu Han, Xiaodong Ma, Jinyong Peng, Min Hu, Zeyao Tang
Methylglyoxal (MGO), an active metabolite of glucose, is observed in high levels in the tissues and blood of diabetic patients. Phosphocreatine (PCr), a high-energy phosphate compound, exhibits a range of pharmacological actions but little is well known of its neuroprotective action. The aim of the present study was to investigate the neuroprotective effects and the possible mechanisms of PCr. Diabetes is closely associated with neurodegenerative diseases, leading not only to the peripheral nervous system (PNS) and but also to central nervous system (CNS) damage...
March 17, 2018: Free Radical Biology & Medicine
Chetna Gangwar, Atul Saxena, Akhil Patel, S P Singh, Sarvajeet Yadav, Ravindra Kumar, Vijay Singh
The experiment was conducted to study cryopreservation induced sperm cryoinjuries and the protective effect of reduced Glutathione supplementation in Murrah bull semen. A total of 20 semen ejaculates were split into two parts after initial examination and were extended in glycerolated egg yolk TRIS diluter (Control group) and glycerolated egg yolk TRIS diluter + 0.5 mM reduced Glutathione (Treatment Group). The diluted semen samples were loaded into 0.25 ml French mini straw and sealing of straws were done...
March 9, 2018: Animal Reproduction Science
Kolla Rajasekhar, Kapilkumar Mehta, Thimmaiah Govindaraju
Amyloid beta (Aβ) aggregation is the key trait responsible for the pathological devastation caused by Alzheimer's disease (AD). Among the various pathways of multifaceted toxicity exhibited by Aβ aggregates in neuronal cells, generation of reactive oxygen species (ROS) by Aβ-CuII complex and mitochondrial damage are prominent. Aβ interferes with mitochondrial transport channels, causing mitochondrial dysfunction. Herein, we present nontoxic hybrid multifunctional modulators (HMMs, TGR86-88) developed by integrating the structural and functional features of the metal chelating aggregation modulator, clioquinol (Clq) and the antioxidant epigallocatechin gallate (EGCG)...
March 20, 2018: ACS Chemical Neuroscience
Ji-Sun Kim, Hyunjung Lee, Chang Hwa Jung, Sung-Joon Lee, Tae-Youl Ha, Jiyun Ahn
Mitochondrial dysfunction is associated with insulin resistance. Although chicoric acid (CA) is known to have beneficial effects on insulin sensitivity, the involvement of mitochondrial function has not been elucidated yet. Here, we investigated the effect of CA on insulin resistance and mitochondrial dysfunction. In palmitate-induced insulin-resistant C2C12 myotubes, CA improved impaired glucose uptake and insulin signaling pathways, along with enhanced mitochondrial membrane potential and oxygen consumption...
March 20, 2018: Bioscience, Biotechnology, and Biochemistry
Yi-Chao Hsu, Yu-Ting Wu, Chia-Ling Tsai, Yau-Huei Wei
In mammalian cells, there are seven members of the sirtuin protein family (SIRT1-7). SIRT1, SIRT6, and SIRT7 catalyze posttranslational modification of proteins in the nucleus, SIRT3, SIRT4, and SIRT5 are in the mitochondria and SIRT2 is in the cytosol. SIRT1 can deacetylate the transcription factor SOX2 and regulate induced pluripotent stem cells (iPSCs) reprogramming through the miR-34a-SIRT1-p53 axis. SIRT2 can regulate the function of pluripotent stem cells through GSK3β. SIRT3 can positively regulate PPAR gamma coactivator 1-alpha (PGC-1α) expression during the differentiation of stem cells...
March 2018: Experimental Biology and Medicine
Tomohiro Kimura, Atsuko Kimura, Mindong Ren, Bob Berno, Yang Xu, Michael Schlame, Richard M Epand
Tafazzin is the mitochondrial enzyme that catalyzes transacylation between a phospholipid and a lysophospholipid in remodeling. Mutations in tafazzin cause Barth syndrome, a potentially life-threatening disease with the major symptom of cardiomyopathy. In the tafazzin-deficient heart, cardiolipin (CL) acyl chains become abnormally heterogeneous unlike those in the normal heart with a single dominant linoleoyl species; tetralinoleoyl CL. In addition, the amount of CL decreases and monolysocardiolipin (MLCL) accumulates...
March 20, 2018: Biochemistry
Soham Sengupta, Rachel Nechushtai, Patricia A Jennings, Jose' N Onuchic, Pamela A Padilla, Rajeev K Azad, Ron Mittler
The iron-sulfur (2Fe-2S) binding motif CDGSH appears in many important plant and animal proteins that regulate iron and reactive oxygen metabolism. In human it is found in CISD1-3 proteins involved in diabetes, obesity, cancer, aging, cardiovascular disease and neurodegeneration. Despite the important biological role of the CDGSH domain, its origin, evolution and diversification, are largely unknown. Here, we report that: (1) the CDGSH domain appeared early in evolution, perhaps linked to the heavy use of iron-sulfur driven metabolism by early organisms; (2) a CISD3-like protein with two CDGSH domains on the same polypeptide appears to represent the ancient archetype of CDGSH proteins; (3) the origin of the human CISD3 protein is linked to the mitochondrial endosymbiotic event; (4) the CISD1/2 type proteins that contain only one CDGSH domain, but function as homodimers, originated after the divergence of bacteria and archaea/eukaryotes from their common ancestor; and (5) the human CISD1 and CISD2 proteins diverged about 650-720 million years ago, and CISD3 and CISD1/2 share their descent from an ancestral CISD about 1-1...
March 19, 2018: Scientific Reports
Klara Habartova, Radim Havelek, Martina Seifrtova, Karel Kralovec, Lucie Cahlikova, Jakub Chlebek, Eva Cermakova, Nadezda Mazankova, Jana Marikova, Jiri Kunes, Lucie Novakova, Martina Rezacova
Scoulerine is an isoquinoline alkaloid, which indicated promising suppression of cancer cells growth. However, the mode of action (MOA) remained unclear. Cytotoxic and antiproliferative properties were determined in this study. Scoulerine reduces the mitochondrial dehydrogenases activity of the evaluated leukemic cells with IC50 values ranging from 2.7 to 6.5 µM. The xCELLigence system revealed that scoulerine exerted potent antiproliferative activity in lung, ovarian and breast carcinoma cell lines. Jurkat and MOLT-4 leukemic cells treated with scoulerine were decreased in proliferation and viability...
March 19, 2018: Scientific Reports
Rowena Schultz, Melanie Krug, Michel Precht, Stefanie G Wohl, Otto W Witte, Christian Schmeer
Müller cells are critical for retinal function and neuronal survival but can become detrimental in response to retinal ischemia and increased oxidative stress. Elevated oxidative stress increases expression of the mitochondrial enzyme frataxin in the retina, and its overexpression is neuroprotective after ischemia. Whether frataxin expression in Müller cells might improve their function and protect neurons after ischemia is unknown. The aim of this study was to evaluate the effect of frataxin overexpression in Müller cells on neuronal survival after retinal ischemia/reperfusion in the mouse in vivo...
March 19, 2018: Scientific Reports
Maria Portia B Nagata, Kenji Endo, Kazuko Ogata, Kenichi Yamanaka, Junki Egashira, Naoto Katafuchi, Tadayuki Yamanouchi, Hideo Matsuda, Yuki Goto, Miki Sakatani, Takuo Hojo, Hirofumi Nishizono, Kenji Yotsushima, Naoki Takenouchi, Yutaka Hashiyada, Kenichi Yamashita
Selection of functional spermatozoa plays a crucial role in assisted reproduction. Passage of spermatozoa through the female reproductive tract requires progressive motility to locate the oocyte. This preferential ability to reach the fertilization site confers fertility advantage to spermatozoa. Current routine sperm selection techniques are inadequate and fail to provide conclusive evidence on the sperm characteristics that may affect fertilization. We therefore developed a selection strategy for functional and progressively motile bovine spermatozoa with high DNA integrity based on the ability to cross laminar flow streamlines in a diffuser-type microfluidic sperm sorter (DMSS)...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
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